Research into Subgroups of Triple Negative Breast Cancer Offers Clues to Treatment

You may have heard that triple negative breast cancer is difficult to treat and wondered how it differs from other forms of breast cancer. Research into triple negative breast cancer is offering clues to more effective treatments.

That diagram of how a cell divides that we saw in high school biology left out some steps. Before a cell can divide, a series of signals pass along a chain of command through proteins until they reach the nucleus and cell division begins. Normally this is an orderly process.

How many types of breast cancer are there?

Cancer is a disease of cells growing out of control. As scientists study the genes and molecular processes involved in normal and cancerous cells, they are finding multiple places where something can go wrong. It seems that every day a researcher is finding a new misstep in cancer cells. Breast cancer isn’t one disease, but many.

It can be labeled by where it starts in the breast — ductal or lobular. Inflammatory breast cancer is a form that grows in the lymph vessels in the skin of the breast. These types can also be labeled by molecular subtype.

The most common one is an estrogen receptor positive tumor. These cells have receptors that take estrogen and feed it to the cell to help it grow. Progesterone receptor positive tumors do the same for the hormone progesterone. All cells in our bodies have a protein called human epidermal growth factor receptor (HER2) that is part of the cell growth process. If a cell has too many of these receptors, it is HER2 positive.

A tumor that tests negative for all these factors is called triple negative (TN). Triple negative tumors tend to be aggressive, and the options for treatment are more limited. Because only about 15 percent of breast cancer is triple negative, less attention has been given to studying it until recently. Several new studies offer hope to TN patients.

Triple negative tumors exhibit even more subgroups

One puzzle for doctors has been the way some TN tumors respond very well to certain types of chemotherapy while others resist it. To understand this problem, scientists have been looking at subgroups within the triple negative category since at least 2011. At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago June 2–6, Jelmar Quist, a Ph.D. candidate at King’s College, London, presented a study with colleagues that analyzed these subgroups to see how they respond to various drugs. The researchers looked at four genes involved in the signaling pathways that tell cells to divide to determine subgroup “signatures.” They tested their theory in 1,368 patients and found that one of the subgroups responded well to platinum-based chemotherapy in metastatic patients. Then they analyzed other patient records to see which subgroups responded best to which drugs.

Next the researchers plan to test their subgroup signatures in a phase III trial of carboplatin compared with docetaxel for patients with metastatic, locally advanced, or BRCA1 and BRCA2 triple negative breast cancer. They hope more information about the subgroups’ responses to various drugs will eventually allow doctors to test triple negative subgroups as routinely as doctors check for hormone status today. Then patients can receive the most appropriate drugs from the start.

Prolactin may be important in understanding triple negative tumors

Researchers at McGill University in Canada are also interested in studying subgroups within triple negative tumors. In the journal Scientific Reports, they explain that cells lacking the prolactin receptor were more aggressive. The scientists looked at information from 580 women with triple-negative breast cancer and found that those whose tumors had the prolactin receptor lived longer. They also studied the effects of prolactin in animal models and found that prolactin can reduce the division of cancer cells. This research may help to explain how breastfeeding reduces breast cancer risk because prolactin is a hormone involved in breastfeeding.

Suhad Ali, the senior author of the study, says that this research may lead to screening for prolactin receptors in breast cancer patients. Prolactin might be used as a single treatment or in combination with chemotherapy to improve outcomes in TN patients.

Clinical trials for TN patients

A July, 2017 article in Oncology Nursing News reports results from four clinical trials for metastatic triple negative patients. Results from the drugs olaparib, ipatasertib, and eribulin appear promising for patients who haven’t had good results from other treatments. Another trial looked at which drug worked best with carboplatin and found that nab-paclitaxel (Abraxane) worked better than the commonly used gemcitabine (Gemzar).

With all the research currently underway, TN patients should ask their doctors about how the research affects them. Because triple negative tumors are only a small portion of breast cancers, you may want to ask for a referral to a comprehensive cancer center or other research hospital that has a specialist in this subtype. A specialist can give you the best advice about more detailed testing of the tumor with the four-gene signature or other genetic profile and direct you to clinical trials when appropriate.